Peripheral Distribution Research Articles

Intra-Amniotic Sildenafil and Rosiglitazone Late in Gestation Ameliorate the Pulmonary Hypertension Phenotype in Congenital Diaphragmatic Hernia

BackgroundPulmonary hypertension remains difficult to manage in congenital diaphragmatic hernia (CDH). Prenatal therapy may ameliorate postnatal pulmonary hypertension. We hypothesized that intra-amniotic (IA) injection of either sildenafil, a phosphodiesterase 5 inhibitor, or rosiglitazone, a PPAR-γ agonist, or both late in gestation would decrease the detrimental pulmonary vascular remodeling seen in CDH and improve peripheral pulmonary blood flow. MethodsPregnant rats were gavaged with nitrogen on embryonic day (E) 9.5 to induce fetal CDH. Sildenafil and/or rosiglitazone were administered to each fetus via an intra-amniotic injection after laparotomy on the pregnant dam at E19.5, and fetuses delivered at E21.5. Efficacy measures were gross necropsy, histology, peripheral blood flow assessment using intra-cardiac injection of a vascular tracer after delivery, and protein expression analysis. ResultsIntra-amniotic injections did not affect fetal survival, the incidence of CDH, or lung weight-to-body weight ratio in CDH fetuses. IA sildenafil injection decreased pulmonary vascular muscularization, and rosiglitazone produced an increase in peripheral pulmonary blood flow distribution. The combination of sildenafil and rosiglitazone decreased pulmonary artery smooth muscle cell proliferation. These intra-amniotic treatments did not show any negative effects in either CDH fetuses or control fetuses. ConclusionIA injection of sildenafil and rosiglitazone late in gestation ameliorates the pulmonary hypertensive phenotype of CDH and may have utility in clinical translation. Level of EvidenceNot applicable.

Is Gender an Important Factor in the Precision Medicine Approach to Levocetirizine?

Currently, there is insufficient information on the variability in levocetirizine pharmacometrics among individuals, a crucial aspect for establishing its clinical use. The gender differences in pharmacokinetics and the extent of variation in pharmacodynamics have not been definitively identified. The primary goal of this study was to investigate gender differences in levocetirizine pharmacokinetics and quantitatively predict and compare how these gender-related pharmacokinetic differences impact pharmacodynamics, using population pharmacokinetic-pharmacodynamic modeling. Bioequivalence results for levocetirizine (only from the control formulation) were obtained from both healthy Korean men and women. Physiological and biochemical parameters for each individual were utilized as pharmacokinetic comparison and modeling data between genders. Pharmacodynamic modeling was performed using reported data on antihistamine responses following levocetirizine exposure. Gender, weight, body surface area, peripheral distribution volume, albumin, central-peripheral inter-compartmental clearance, and the fifth sequential absorption rate constant were explored as effective covariates. A comparison of the model simulation results showed a higher maximum concentration and faster plasma loss in females than in males, resulting in a faster recovery to baseline of the antihistamine effect; however, the absolute differences between genders in the mean values were not large within 10 ng/mL (for plasma concentrations) or % (wheal and flare size changes). Regarding the pharmacokinetics and pharmacodynamics of levocetirizine, the gender effect may not be significant when applying the usual dosage (5 mg/day). This study will be useful for bridging the knowledge gap in scientific precision medicine by introducing previously unconfirmed information regarding gender differences in levocetirizine pharmacometrics.

Peripheral blood regulatory B and T cells are decreased in patients with focal epilepsy

Patients with focal epilepsy of unknown cause (FEoUC) may display T cell infiltration in post-surgery brain specimens and increased serum levels of pro-inflammatory cytokines produced by B and T cells, indicating potential involvement of adaptive immunity. Our study aimed to investigate the peripheral blood distribution of B and T cell subgroups to find clues supporting the distinct organization of adaptive immunity in FEoUC. Twenty-two patients with FEoUC and 25 age and sex matched healthy individuals were included. Peripheral blood mononuclear cells were immunophenotyped by flow cytometry. Expression levels of anti-inflammatory cytokines and FOXP3 were measured by real-time PCR. Carboxyfluorescein succinimidyl ester (CFSE) proliferation assay was conducted using CD4+ T cells. Patients with FEoUC showed significantly decreased regulatory B (Breg), B1a, plasmablast and regulatory T (Treg) cell percentages, and increased switched memory B and Th17 cell ratios. Moreover, CD4+CD25+CD49d− Tregs of FEoUC patients displayed significantly reduced TGFB1 and FOXP3, but increased IL10 gene expression levels. CD4+ helper T cells of patients with FEoUC gave more exaggerated proliferation responses to phytohemagglutinin, anti-CD3 and anti-CD28 stimulation. Patients with FEoUC display increased effector lymphocyte, decreased regulatory lymphocyte ratios, and impaired Treg function and enhanced lymphocyte proliferation capacity. Overall, this pro-inflammatory phenotype lends support to the involvement of adaptive immunity in FEoUC.

Effect of Oligopin Administration on Ovarian Morphology in Women with Polycystic Ovarian Syndrome (PCOS)

Background. The effects of oligopin as an antioxidant on polycystic ovarian morphology (PCOM) have not yet been examined. Therefore, the objective of this study was to evaluate the oligopin supplementation on PCOM among patients with polycystic ovarian syndrome (PCOS). Methods. This randomized, placebo‐controlled trial was carried out at Shariati Hospital, Arash Hospital, and Yas Hospital, Tehran, Iran, to determine the effect of oligopin (50 mg/d) or placebo in PCOS patients. The ultrasonographic ovarian morphology was assessed in women aged 18–40 years, before and after 3 months of intervention. Results. Among 45 randomized participants, 32 participants, of whom 17 were in the oligopin group and 15 were in the placebo group completed the trial. There was only one adverse event in the oligopin group. The mean (standard deviation) age of the patients was 30.47 (6.30) years and the median (interquartile range) BMI was 27.50 (23.42–33.55). Three months of oligopin therapy significantly decreased ovarian stromal area (p = 0.01) and stromal/total area (p = 0.003). However, no significant differences were observed in the ovarian volume, ovarian area, 2–9 mm antral follicle counts, or peripheral follicle distribution pattern at 3 months. Conclusion. Among participants with PCOS, the use of oligopin (50 mg) daily, as compared with a placebo, resulted in improvement of the stromal area and stromal/total area at the end of the 3 months of treatment. Further studies are, however, needed to evaluate the longer‐term efficacy and safety. This trial is registered with IRCT20140406017139N3.

Inhaled Corticosteroids Particle Size and Risk of Hospitalization Due to Exacerbations and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Nationwide Cohort Study.

Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear. This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis. Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82-1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85-1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63-0.82, p<0.001) and all-cause mortality (HR 0.72, 95% CI 0.61-0.86, p<0.001). The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.

Population pharmacokinetic modeling of levodropropizine: extended application to comparative analysis between commercial formulations and exploration of pharmacokinetic effects of diet.

Levodropropizine, a nonopioid antitussive agent, is being increasingly used in clinical practice with the development of several formulations for symptomatic relief of acute and chronic bronchitis. However, scientific and quantitative population pharmacokinetic analyses of levodropropizine are lacking. Moreover, no integrated quantitative comparison has been performed between formulations. This study quantitatively evaluated and predicted pharmacokinetic properties of formulations through population pharmacokinetic model-based comparisons of commercially available formulations. Plasma concentration profile results from bioequivalence studies of 60-mg immediate release (IR) levodropropizine tablets in 40 healthy Korean males were used as population pharmacokinetic modeling data. For interindividual variability in levodropropizine pharmacokinetics, body surface area was identified as an effective covariate that was positively correlated with peripheral compartment distribution volume. Population pharmacokinetic model for IR tablets well-described the levodropropizine syrup and capsule datasets, suggesting no significant differences in pharmacokinetics among IR tablets, syrups, and capsules of levodropropizine. In contrast, pharmacokinetic profiles differed between 90-mg controlled release (CR) and IR levodropropizine tablets; however, separate parameter estimation was possible by applying the same model structure. In terms of pharmacokinetics, twice-daily regimen of 90-mg CR tablets was equivalent to thrice-daily regimen of 60-mg IR tablets. However, at steady-state, interindividual plasma concentration variability within population was reduced by approximately 36.71-83.18%. For levodropropizine CR tablets, a high-fat diet significantly delayed gastrointestinal absorption but maintained overall plasma exposure equivalent. This study provides useful quantitative judgment data for precision medicine of levodropropizine and can be helpful in predicting the pharmacokinetics of levodropropizine based on commercialized formulation switching.

#313 : The Correlation Between Ultrasound Morphological Parameters and Phenotypes of Polycystic Ovary Syndrome in Indonesian Women

Background and Aims: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that affects women of reproductive age. Ultrasound morphological parameters of ovarian morphology, ovarian volume, follicle number, endometrial plate thickness, and doppler analysis are necessary for the diagnosis of PCOS. The aim of this study is to evaluate the correlation between ultrasound morphological parameters and classic and nonclassic phenotypes of PCOS in Indonesian Women. Method: A single-center, observational analytic study from May 2022 until October 2022 was performed upon 50 women with PCOS at Halim Fertility Center (HFC), Indonesia. Fifty PCOS women were classified into two groups: 20 PCOS women with classic phenotype and 30 PCOS women with non-classic phenotype. Data on patient’s age, body mass index (BMI), LH level, FSH level, LH: FSH ratio, Testosterone, Free testosterone index, SHBG, HOMA-IR, Ultrasound parameters (antral follicle count, follicle size, ovarian volume, stromal volume, Stromal/total area (S/A) ratio, Pulsatility index (PI), Peak systolic velocity (PS) and follicle distribution) were assessed and compared between the two groups. Results: The antral follicle count was higher in classic phenotype of PCOS than in nonclassic phenotype and there was a significant difference between the groups (p&lt;0.05). The stromal volume and PI were higher in non-classic phenotype PCOS than in classic phenotype and there was significantly difference between the groups (p&lt;0.05). Most of the follicle distribution in the classic phenotype of PCOS was central and the follicle distribution in the non-classic phenotype was peripheral and there was significantly difference between the groups (p&lt;0.05). The number of antral follicles, stromal volume, PI, and follicle distribution were positively correlated with the PCOS phenotypes (r=0.734; r=0.594; r=0.577; r=0.196), respectively. Conclusion: Classic phenotype of PCOS in Indonesian women has high antral follicle count and central follicle distribution and nonclassic phenotype has high stromal volume, PI and peripheral follicle distribution.

Doping-induced assembly interface for noninvasive in vivo local and systemic immunomodulation.

Peripheral neural interfaces, potent in modulating local and systemic immune responses for disease treatment, face significant challenges due to the peripheral nerves' broad distribution in tissues like the fascia, periosteum, and skin. The incongruity between static electronic components and the dynamic, complex organization of the peripheral nervous system often leads to interface failure, stalling circuit research and clinical applications. To overcome these, we developed a self-assembling, tissue-adaptive electrode composed of a single-component cocktail nanosheet colloid, including dopants, conducting polymers, stabilizers, and an MXene catalyst. Delivered via a jet injector to designated nerve terminals, this assembly utilizes reactive oxygen species to catalytically dope poly (3,4-ethylenedioxythiophene), enhancing π-π interactions between nanosheets, and yielding a conductive, biodegradable interface. This interface effectively regulates local immune activity and promotes sensory and motor nerve functional restoration in nerve-injured mice, while engaging the vagal-adrenal axis in freely moving mice, eliciting catecholamine neurotransmitter release, and suppressing systemic cytokine storms. This innovative strategy specifically targets nerve substructures, bolstering local and systemic immune modulation, and paving the way for the development of self-adaptive dynamic neural interfaces.

Effect of granular shape on radial segregation in a two-dimensional drum

Granular segregation is widely observed in nature and industry. Most research has focused on segregation caused by differences in the size and density of spherical grains. However, due to the fact that grains typically have different shapes, the focus is shifting towards shape segregation. In this study, experiments are conducted by mixing cubic and spherical grains. The results indicate that spherical grains gather at the center and cubic grains are distributed around them, and the degree of segregation is low. Through experiments, a structured analysis of local regions is conducted to explain the inability to form stable segregation patterns with obviously different geometric shapes. Further, through simulations, the reasons for the central and peripheral distributions are explained by comparing velocities and the number of collisions of the grains in the flow layer.

Developing radiology diagnostic tools for pulmonary fibrosis using machine learning methods

BackgroundAccurate and prompt diagnosis of the different patterns for pulmonary fibrosis is essential for patient management. However, accurate diagnosis of the specific pattern is challenging due to overlapping radiographic characteristics. Materials and methodsWe conducted a retrospective chart review utilizing two machine learning methods, classification and regression tree and Bayesian additive regression tree, to select the most important radiographic features for diagnosing the three most common fibrosis patterns and created an online diagnostic app for convenient implementation. ResultsFour hundred patients (median age of 67 with inter quartile range 58–73; 200 males) were included in the study. Peripheral distribution, homogeneity, lower lobe predominance and mosaic attenuation of fibrosis are the four most important features identified. Bayesian additive regression tree demonstrates better performance than classification and regression tree in diagnosis prediction and provides the predicted probability of each diagnosis with uncertainty intervals for each combination of features. ConclusionThe model and app built with Bayesian additive regression tree can be used as an effective tool in assisting radiologists in the diagnostic process of pulmonary fibrosis pattern recognition.

LM-DNN: pre-trained DNN with LSTM and cross Fold validation for detecting viral pneumonia from chest CT

ABSTRACT Some of the viruses may cause lung parenchyma and airway involvement. Usually, viral pneumonia causes ground-glass opacities, bilateral peripheral distribution, consolidation, vascular thickening, and reticular opacity. These features are common in COVID-19 rather than Non-Covid-19 viral pneumonia. However, in advanced cases, COVID-19 viral pneumonia may cause organising pneumonia and fibrosis of the lung. Atypical findings of Non-Covid-19 pneumonia have included central peripheral distribution, pleural effusion, lymphadenopathy, nodules, tree-in-bud opacities, and pneumothorax. Therefore, differentiating Non-Covid-19 pneumonia from COVID-19 pneumonia at chest computed tomography (CT) is necessary. In that case, CT scans of the thorax are one of the essential tools for early identification and future prognosis of viral pneumonia. We have proposed a Computer-Aided Diagnostic (CAD) system that can detect features of chest CT using a Deep Neural Network (DNN) with Long Short-Term Memory (LSTM). Transfer learning using pre-trained DNN models (ResNet50, VGG19, InceptionV3, Xception, DenseNet121, and VGG16) is applied to retain both high-level and low-level features effectively. The deep features are passed to the LSTM layer. The LSTM is utilised as a classifier and detects long short-term dependencies. The proposed method employs a hybrid DNN-LSTM network for automatic detection to take advantage of the uniqueness of the two models. The proposed models are trained with common and different features present in the chest CT of COVID-19 and Non-Covid-19 viral pneumonia. The 5-fold cross-validation (CV) method validated and tested the proposed model. The proposed DNN model’s performance is quite improved with LSTM and CV. As a result, the proposed LM-DNN (VGG16+LSTM+CV) model has achieved the classification test accuracy of 91.58% and specificity of 93.86%, which offers superior performance with state-of-the-art. Also, the DenseNet121+LSTM+CV model has reached the classification test accuracy of 90.1% and sensitivity of 92%.

Peripheral reactions and elastic scattering induced by strongly bound, weakly bound and exotic nuclei

A phenomenological study of peripheral reactions induced by strongly bound, weakly bound and exotic projectiles on different targets is presented. A large number of experimental elastic scattering differential cross sections at energies close to the Coulomb barrier is studied on the basis of a simple nuclear optical model potential that depends on a small number of parameters. The derived wave functions, together with the imaginary component of the optical potential, allow the analysis of the radial peripheral absorption density distributions for the different kind of projectiles. These distributions, when appropriately normalized, show a clear correlation with the type of projectile regardless of the involved target and indicate that projectiles more prone to break up show a more peripheral absorption density distribution. This manifests in their magnitude, location and width. The relationship of these variables in the strongly bound group and the weakly bound group are described with a simple exponential function, while the exotic projectiles show two distinct groups, namely the neutron-halo and the proton-halo. For the neutron-halo projectiles such as He6, Li11 and Be11 there is a notable increment of the radial peripheral absorption density peak and the total reaction cross section as the breakup separation energy decreases. The same relationship is established for the proton-halo projectiles B8 and F17 but their reduced effective dipole charge leads to a lower probability of dipole Coulomb breakup that results in a substantial reduction in the extent of their peripheral absorption.

Sensory disturbances in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

Abnormal immune function of B lymphocyte in peripheral blood of Parkinson's disease

BackgroundParkinson's disease (PD) is associated with peripheral inflammation and abnormal peripheral blood lymphocyte immune responses. Peripheral blood B-lymphocyte subset distributions and whether they are associated with PD are unclear. MethodsSixty-one PD patients and sixty-one one-to-one paired healthy controls (HCs) were enrolled. We used flow cytometry to perform immunophenotyping of peripheral B-lymphocyte, in vitro stimulation and measured serum cytokine. The relationship between variables and PD were assessed. ResultsThe percentage of naive B cells in blood of PD patients was decreased, whereas the percentages of regulatory B cells (Bregs), plasma blast cells (PBCs), and double-negative (DN) B cells were increased. The absolute counts of B-lymphocyte and naive B cells in blood of PD patients were decreased. Regression analysis revealed that alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells were associated with PD. After stimulation, the percentages of Bregs, PBCs, and switched memory (SwM) B cells increased in PD patients. Additionally, increases in GM-CSF-producing B-cell, IFN-γ-producing B-cell, and TNF-α-producing B-cell percentages were noted in PD. Serum levels of a proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and soluble CD40 ligand (sCD40L) were elevated in PD and correlated negatively with the UPDRS III score. ConclusionsAbnormal B-lymphocyte immune responses in peripheral blood may contribute to PD development. Alterations in the absolute counts of B-lymphocyte and the percentage of Bregs and DN B cells are associated with PD. Furthermore, APRIL, BAFF, and sCD40L could be potential targets for intervention in PD.

Intra-urban differences underlying leprosy spatial distribution in central Brazil: geospatial techniques as potential tools for surveillance.

This ecological study identified an aggregation of urban neighbourhoods spatial patterns in the cumulative new case detection rate (NCDR) of leprosy in the municipality of Rondonópolis, central Brazil, as well as intra-urban socioeconomic differences underlying this distribution. Scan statistics of all leprosy cases reported in the area from 2011 to 2017 were used to investigate spatial and spatiotemporal clusters of the disease at the neighbourhood level. The associations between the log of the smoothed NCDR and demographic, socioeconomic, and structural characteristics were explored by comparing multivariate models based on ordinary least squares (OLS) regression, spatial lag, spatial error, and geographically weighted regression (GWR). Leprosy cases were observed in 84.1% of the neighbourhoods of Rondonópolis, where 848 new cases of leprosy were reported corresponding to a cumulative NCDR of 57.9 cases/100,000 inhabitants. Spatial and spatiotemporal high-risk clusters were identified in western and northern neighbourhoods, whereas central and southern areas comprised low-risk areas. The GWR model was selected as the most appropriate modelling strategy (adjusted R²: 0.305; AIC: 242.85). By mapping the GWR coefficients, we identified that low literacy rate and low mean monthly nominal income per household were associated with a high NCDR of leprosy, especially in the neighbourhoods located within high-risk areas. In conclusion, leprosy presented a heterogeneous and peripheral spatial distribution at the neighbourhood level, which seems to have been shaped by intra-urban differences related to deprivation and poor living conditions. This information should be considered by decision-makers while implementing surveillance measures aimed at leprosy control.

BSLD-01 DYNAMIC CONTROL OF CSF FOR PERSONALIZED CNS DRUG DELIVERY FOR LEPTOMINGEAL DISEASE

Abstract BACKGROUND Appropriate drug distribution is needed for effective treatment of brain metastases and leptomeningeal disease. Lack of proper drug bioavailability in the CNS contributes to the poor outcome in these patients. EnClear Therapies has developed a device delivering intrathecal therapeutics utilizing the dynamic control of CSF flow through an external pump. Herein, we look at intrathecal drug delivery of methotrexate with EnClear’s system and its impact of drug concentration in CNS tissue in sheep and non-human primates. METHODS EnClear’s system utilizes two implantable catheters (lateral ventricle and lumbar thecal sac) and an extracorporeal pump that controls the speed and direction of CSF flow. Software continuously monitors and reports the output from sensor arrays for pressure, respiration, and heart rate. Imaging studies were used to track the CSF flow characteristics during the use of EnClear’s system. Data from administration of methotrexate followed by the use of EnClear’s system was compared to the current standard of delivery, intracerebroventricular or lumbar intrathecal administration. Methotrexate levels were measured with LC/MS in CSF, blood, and multiple CNS and peripheral tissues. RESULTS There was a two-fold increase in methotrexate levels in multiple regions of the brain including deeper brain structures including the striatum using EnClear's system, compared to traditional lumbar intrathecal and intracerebroventricular delivery. Higher peak levels of methotrexate were reached in the CSF with the use of EnClear’s system, with simultaneous reduction in the peripheral nerves and systemic tissues – a potential source of toxicity. CONCLUSIONS In large animal studies, EnClear’s system has for the first time, demonstrated increased brain parenchymal drug levels via intrathecal delivery. Drug delivery with this novel device has shown improved distribution throughout the CNS and leptomeninges as compared to traditional intrathecal drug delivery and decreased peripheral distribution.

A Gain-Enhanced Differential-Fed Stacked Circular Patch Antenna With Simultaneously Controllable E-Plane and H-Plane Radiation Nulls

In this work, a differential-fed three-layer stacked circular patch antenna with enhanced gain performance is theoretically investigated for the simultaneous control of radiation nulls over both <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">E</i> -plane and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</i> -plane patterns. First, the bottom layer patch is meticulously designed based on a modified TM <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">11</sub> mode to meet the matching conditions. Then, the structures of the parasitic layer patches are contrived to form similar peripheral radiative current distributions compared with the bottom one, aiming to simplify the analysis process. After that, the three-layer patches are stacked in a capacitively coupled fashion, which guarantees the out-of-phase scheme between the middle layer patch and the other two-layer patches. By means of the cavity-model theorem, further investigations on the multilayer distributions of the equivalent magnetic currents for the three radiators have successfully demonstrated that the destructive interference among the currents will result in the emergence of radiation nulls for both <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">E</i> -plane and <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">H</i> -plane patterns. As a result, the beamwidth of the antenna in the two principal planes can be narrowed, which contributes to a significant improvement in the overall gain performance. Furthermore, a thorough array factor analysis on the flexible control of the radiation nulls is highlighted with both theoretical predictions and full-wave quantitative verifications. Finally, an experimental prototype is fabricated and measured to prove its validity. Compared with other stacked antennas with approximately the same longitudinal profiles, this design features the highest measured peak gain of 13.9 dBi, with an attractive increment of 8.0 dB pronounced.

Unmasked Neuropathic Pain After Neurectomy: A Case Series and Review of the Literature

Summary: Localization of neuropathic pain to a specific peripheral nerve origin relies on patient history, physical examination, and nerve blocks. Neurectomy of the involved nerve(s) can successfully alleviate patients’ pain. However, a subset of patients postoperatively describe persistent pain, but say that the pain “moved” to a new location (eg, from the dorsum of the foot to the lateral foot). This may be viewed as a treatment failure by the patient and surgeon alike. Further investigation, however, may localize the new pain to an additional, separate peripheral nerve injury, which was previously unrecognized by both parties. The mechanism involved is that of pain masking and unmasking. Successful treatment of the more prominent pain stimulus allows for recognition of a second, less-offending peripheral nerve injury. As the field of surgical treatment of chronic peripheral neuropathic pain advances, it is important to identify and define specific nuances of diagnosis and treatment via neurectomy. The term “diffuse noxious inhibitory control,” used to describe the pain-inhibits-pain pathway, may help explain the phenomenon of masking, whereby one pain generator is more prominent and shields another site from recognition and subsequent diagnosis. In this context, unmasked pain should be considered as a potential source of surgical treatment failure. We present a series of patients who, following improvement in the initial location of their pain, reported pain in a distinctly new peripheral nerve distribution, leading to reoperation.

Quantitative chest CT imaging characteristics and outcome of patients with COVID-19 associated pulmonary artery thrombosis: A single-center retrospective cohort study.

Coronavirus disease 2019 (COVID-19)-associated pulmonary thrombotic events occur frequently and are associated with disease severity and worse clinical outcomes. We aimed to describe the clinical and quantitative chest computed tomography (CT) imaging characteristics based on density ranges (Hounsfield units) and the outcomes of patients with COVID-19 associated pulmonary artery thrombosis. This retrospective cohort study included all patients with COVID-19 hospitalized in a tertiary care hospital between March 2020 and June 2022 who underwent a CT pulmonary angiography. We included 73 patients: 36 (49.3%) with and 37 (50.7%) without pulmonary artery thrombosis. The in-hospital all-cause mortality was 22.2 versus 18.9% ( P = .7), and the intensive care unit admission rates were 30.5 versus 8.1% ( P = .01) at the time of diagnosis of pulmonary artery thrombosis. Except for D-dimers (median of 3142 vs 533, P = .002), the other clinical, coagulopathy, and inflammatory markers were similar. Logistic regression analysis revealed that only D-dimers were associated with pulmonary artery thrombosis ( P = .012). ROC curve analysis of D-dimers showed that a value greater than 1716 ng/mL predicted pulmonary artery thrombosis with an area under the curve of 0.779, 72.2% sensitivity, and 73% specificity (95% CI 0.672-0.885). Peripheral distribution of pulmonary artery thrombosis was recorded in 94.5% of cases. In the lower lobes of the lungs, the incidence of pulmonary artery thrombosis was 6 times higher than that in the upper lobes (58-64%), with a percentage of lung injury of 80% to 90%. Analysis of the distribution of arterial branches with filling defects revealed that 91.6% occurred in lung areas with inflammatory lesions. Quantitative chest CT imaging provides valuable information regarding the extent of COVID-19 associated lung damage and can be used to anticipate the co-location of pulmonary immunothrombotic events. In patients with severe COVID-19, in-hospital all-cause mortality was similar regardless of the presence of associated distal pulmonary thrombosis.

Liver Cancer Vascularity Driven by Extracellular Matrix Stiffness: Implications for Imaging Research.

Extracellular matrix stiffness represents a barrier to effective local and systemic drug delivery. Increasing stiffness disrupts newly formed vessel architecture and integrity, leading to tumor-like vasculature. The resulting vascular phenotypes are manifested through different cross-sectional imaging features. Contrast-enhanced studies can help elucidate the interplay between liver tumor stiffness and different vascular phenotypes. This study aims to correlate extracellular matrix stiffness, dynamic contrast-enhanced computed tomography, and dynamic contrast-enhancement ultrasound imaging features of 2 rat hepatocellular carcinoma tumor models. Buffalo-McA-RH7777 and Sprague Dawley (SD)-N1S1 tumor models were used to evaluate tumor stiffness by 2-dimensional shear wave elastography, along with tumor perfusion by dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography. Atomic force microscopy was used to calculate tumor stiffness at a submicron scale. Computer-aided image analyses were performed to evaluate tumor necrosis, as well as the percentage, distribution, and thickness of CD34+ blood vessels. Distinct tissue signatures between models were observed according to the distribution of the stiffness values by 2-dimensional shear wave elastography and atomic force microscopy ( P < 0.05). Higher stiffness values were attributed to SD-N1S1 tumors, also associated with a scant microvascular network ( P ≤ 0.001). Opposite results were observed in the Buffalo-McA-RH7777 model, exhibiting lower stiffness values and richer tumor vasculature with predominantly peripheral distribution ( P = 0.03). Consistent with these findings, tumor enhancement was significantly greater in the Buffalo-McA-RH7777 tumor model than in the SD-N1S1 on both dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography ( P < 0.005). A statistically significant positive correlation was observed between tumor perfusion on dynamic contrast-enhanced ultrasonography and contrast-enhanced computed tomography in terms of the total area under the curve and % microvessel tumor coverage ( P < 0.05). The stiffness signatures translated into different tumor vascular phenotypes. Two-dimensional shear wave elastography and dynamic contrast-enhanced ultrasonography adequately depicted different stromal patterns, which resulted in unique imaging perfusion parameters with significantly greater contrast enhancement observed in softer tumors.